Pyrimidine compound as JAK kinase inhibitor
Inventors
Kozak, Jennifer • Hudson, Ryan • Brandt, Gary E. L. • McKinnell, Robert Murray • Dabros, Marta • Nzerem, Jerry
Assignees
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Publication Number
US-12172994-B2
Publication Date
2024-12-24
Expiration Date
Abstract
The invention provides a compound of formula (I):or a pharmaceutically-acceptable salt thereof, that is an inhibitor of JAK kinases. The invention also provides pharmaceutical compositions comprising such compound, a crystalline form, methods of using such compound to treat inflammatory skin diseases and other diseases, and processes and intermediates useful for preparing such compound.
Core Innovation
The invention characterizes crystalline Form II, an anhydrous freebase form of pyrimidine JAK inhibitor compound (I), by powder X-ray diffraction peaks at 2θ values of 11.4° and 21.9°. The crystalline form exhibits a differential scanning calorimetry endotherm at 238.1 ± 2°C and demonstrates non-hygroscopic properties with about 0.02% moisture uptake over 5–90% relative humidity. The disclosure additionally references crystalline Form I, though the background problem is not explicitly described.
The disclosure reports potent inhibition of JAK1, JAK2, JAK3, and TYK2 alongside topical skin activity for compound (I). Documented findings include inhibition of CXCL10 expression ex vivo in human skin, inhibition of IL-31-induced pSTAT3 in mice, and skin deposition with plasma levels below quantitation in mini-pigs. These reported findings describe target engagement and local tissue exposure without specifying an addressed technical problem.
Claims Coverage
The claim coverage includes one inventive feature directed to a crystalline form of compound (I).
Crystalline form characterized by powder X-ray diffraction peaks
A crystalline form of the compound of formula (I), characterized by a powder X-ray diffraction pattern comprising diffraction peaks at 2θ values of 11.4±0.2 and 21.9±0.2, wherein dependent claims further specify the crystalline form, pharmaceutical compositions, and methods of treatment.
The independent claim covers the crystalline form characterized by the recited diffraction peaks, with dependent claims covering pharmaceutical compositions and the treatment of inflammatory or autoimmune skin diseases.
Stated Advantages
Form II is reported as non-hygroscopic, exhibiting about 0.02% moisture uptake across 5–90% relative humidity.
The disclosure reports potent JAK inhibition and topical skin activity, including inhibition of CXCL10 expression ex vivo in human skin and inhibition of IL-31-induced pSTAT3 in mice.
The disclosure reports substantial skin deposition with plasma levels below quantitation in mini-pigs.
Documented Applications
Pharmaceutical compositions containing the crystalline form and a pharmaceutically acceptable carrier, including topical formulations.
Treatment of inflammatory or autoimmune skin diseases, including atopic dermatitis.
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